{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:57:21Z","timestamp":1790834241417,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Sodium\u2010glucose cotransporter\u20102 (SGLT\u20102) inhibitors have become a key drug class in the treatment of Type 2 diabetes (T2D) due to their effectiveness in blood sugar control, but also for many other clinical indications because of beneficial effects on cardiovascular diseases and mortality. Therefore, the findings of a secondary analysis of the recent EMMY trial, in which acute myocardial infarction patients treated with empagliflozin had higher trimethylamine\u2010N\u2010oxide (TMAO) serum levels compared to placebo, were unexpected, as high TMAO concentrations in blood have previously been linked to adverse cardiovascular and mortality outcomes. In light of this, the aim of our study was to explore the effects of the SGLT\u20102 inhibitors empagliflozin and dapagliflozin on plasma concentrations and renal clearance (Cl\n                      <jats:sub>R<\/jats:sub>\n                      ) in a T2D patient setting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Plasma and 24\u2010h urine samples from two prospective, randomised, placebo\u2010controlled, double\u2010blind, cross\u2010over trials with T2D patients (empagliflozin\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200969, NCT02471963; dapagliflozin\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200954, NCT02383238), taken at baseline and after each treatment with either SGLT\u20102 inhibitor or placebo, were measured for TMAO via LC\u2013MS\/MS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After treatment with an SGLT\u20102 inhibitor, in the total of 123 patients, TMAO plasma levels were 11.5% higher compared to placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006) and Cl\n                      <jats:sub>R<\/jats:sub>\n                      of TMAO was reduced by 10.3% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.048) without any relevant change in its urinary excretion (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.521). In the dapagliflozin trial, TMAO plasma concentration was 23.4% higher (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.021), and Cl\n                      <jats:sub>R<\/jats:sub>\n                      of TMAO was 22.6% lower (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025) after treatment with dapagliflozin compared to placebo. For empagliflozin, a similar trend was observed, but did not reach statistical significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Treatment with an SGLT\u20102 inhibitor was associated with a modest increase in plasma concentration of TMAO. Together with data from a previous trial, the present findings suggest a possible class effect of SGLT\u20102 inhibitors. Whether this effect impacts the overall clinical benefits of SGLT\u20102 inhibitors needs to be subject to further investigations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      : NCT02471963 (registered 15th June 2015, retrospectively registered) and NCT02383238\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70318","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:03:24Z","timestamp":1790831004000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of\n                    <scp>SGLT<\/scp>\n                    \u20102 Inhibitors on Plasma Concentrations and Renal Clearance of the Risk Marker Trimethylamine\u2010N\u2010Oxide in Patients With Type\u20102 Diabetes"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5530-5629","authenticated-orcid":false,"given":"Katja B.","family":"Zimmer","sequence":"first","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1729-4231","authenticated-orcid":false,"given":"Arne","family":"Gessner","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"FAU NeW \u2013 Research Center New Bioactive Compounds Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Kannenkeril","sequence":"additional","affiliation":[{"name":"Department of Medicine 4 \u2013 Nephrology and Hypertension Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Medicine 4 \u2013 Nephrology and Hypertension Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6873-5332","authenticated-orcid":false,"given":"Armin","family":"Str\u00f6bel","sequence":"additional","affiliation":[{"name":"Center for Clinical Studies Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland 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